Journal article

Novel mechanisms of apoptosis induced by histone deacetylase inhibitors

MJ Peart, KM Tainton, AA Ruefli, AE Dear, KA Sedelies, LA O'Reilly, NJ Waterhouse, JA Trapani, RW Johnstone

Cancer Research | AMER ASSOC CANCER RESEARCH | Published : 2003

Abstract

Histone deacetylase inhibitors (HDACIs) are a new class of chemotherapeutic drugs able to induce tumor cell apoptosis and/or cell cycle arrest; however, the molecular mechanisms underpinning their anticancer effects are poorly understood. Herein, we assessed the apoptotic pathways activated by three HDACIs, suberoylanilide hydroxamic acid, oxamflatin, and depsipeptide. We determined that all three drugs induced the accumulation of cells with a 4n DNA content and apoptosis mediated by the intrinsic apoptotic pathway. HDACI-induced mitochondrial membrane damage and apoptosis were inhibited by overexpression of Bcl-2, but not by the polycaspase inhibitor N-tert-butoxy-carbonyl-Val-Ala-Asp-fluor..

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